[Treatment mapping of lower urinary tract symptoms due to benign prostatic hyperplasia-an analysis of the Governing Body of German Prostate Centers]. / Versorgungsabbild des benignen Prostatasyndroms ­ eine Analyse des Dachverbandes der Prostatazentren Deutschlands (DVPZ) e. V.

BACKGROUND: Due to the high incidence and demographic development, there is an urgent need for healthcare research data on lower urinary tract symptoms due to benign prostatic hyperplasia (LTUS/BPH). Since 2005 the Governing Body of German Prostate Centers (DVPZ) has been collecting data from 22 prostate centers in order to determine the quality and type of cross-sectoral care in particular for LUTS/BPH patients. OBJECTIVES: Presentation of the DVPZ database in general, as well as an investigation of treatment patterns for medical and instrumental therapies. MATERIALS AND METHODS: The analysis is based on UroCloud data sets from 30 November 2017. In the UroCloud data on diagnostics, therapy and course of disease are recorded in a web-based manner. RESULTS: A total of 29,555 therapies were documented for 18,299 patients (1.6/patient), divided into 48.5% instrumental, 29.2% medical treatment, and 18.0% "wait and see" (in 4.3% no assignment was possible). Patients treated with an instrumental therapy were oldest (median: 72 years, interquartile range: 66-77), had the largest prostate volumes (50 ml, 35-75 ml), and were mostly bothered by symptoms (International Prostate Symptom Score = 19/4). The majority of patients under medical treatment received alphablockers (56%); phytotherapeutics were used least frequently (3%). Instrumental therapies are dominated by transurethral resection (TUR) of the prostate (60.0%), open prostatectomy (9.4%) and laser therapy (5.0%), with laser therapy having the shortest hospital stay (5 days) and the lowest transfusion and re-intervention rates (1.0% and 4.6%, respectively). CONCLUSIONS: The DVPZ certificate covers the complete spectrum of cross-sectoral care for LUTS/BPH patients and documents the use of the various therapies as well as their application and effectiveness in the daily routine setting.

Malignant mixed mullerian tumor of the urinary bladder in a 73 year old woman.

A giant tumor of the urinary bladder in a 73 year old female patient consisting of mesenchymal and epithelial parts turned out to be the first case of a Malignant Mixed Muellerian tumor of the urinary bladder.

[DiaPat urine test for prostate cancer. Predictive value for results of transrectal ultrasound-guided prostate biopsies]. / DiaPat-Prostatakarzinom-Urintest. Vorhersagekraft für das Ergebnis transrektal-sonographisch gesteuerter Prostatabiopsien.

BACKGROUND: A novel urine test for early detection of prostate cancer (PCA), distributed and marketed by the company DiaPat, is advertised by the statement "correct analysis in 9 of 10 cases." PATIENTS AND METHODS: The test separates urinary polypeptides by means of capillary electrophoresis and characterizes the peptides in a time-of-flight mass spectrometer. The DiaPat test was performed on the urine of 18 men prior to multiple ultrasound-guided prostate biopsies. RESULTS: Sixteen of the 18 samples met the requirements for sample quality as established by the manufacturer. Eight of these 16 urine samples had been collected from patients in whom biopsies consecutively detected PCA; the remaining eight patients had benign biopsy results. Among the eight patients with detected PCA, the urine test yielded a low probability for PCA in three cases and a high probability in five. Within the group of eight patients with benign biopsy results, the urine test predicted a high probability for PCA in five men and a low probability in three. For the given PCA incidence of 50% within the investigated population, the DiaPat test correctly predicted biopsy results in one half of the population, whereas prediction in the remaining half was incorrect. CONCLUSION: Unless reliable validation of the DiaPat urine test for PCA is available, no clinical consequences should be drawn from the test results.

Implementation of a map in radical prostatectomy specimen allows visual estimation of tumor volume.

INTRODUCTION: Tumor volume is one of the best documented prognostic factors for prostate cancer. There are several methods to gain this important parameter but unfortunately most of the clinicians in the world do not get this information in their routine practice from the pathologist. We developed a standardized method to handle radical prostatectomy specimens including a special form of mapping in order to document relevant morphological data. The aim of this study was to investigate if our model of mapping prostate cancer, which we use in routine practice, may serve for visual estimation of tumor volume. METHODS: We estimated the tumor volume of prostate cancer by visual estimation of 350 maps of radical prostatectomy specimens and correlated these data with established prognostic parameters and clinical outcome. RESULTS: Significant correlations between tumor volumes, as obtained from our mapping, and known prognostic parameters such as preoperative serum levels of prostatic specific antigen, loss of differentiation, histological grade, lymph node metastasis, and margins were found. In a multivariate analysis, only Gleason score and tumor stage were shown to be independent prognostic parameters. DISCUSSION: We demonstrate that mapping of prostate cancer is more than a simple method of documentation but may serve as a method for visual estimation of tumor volume of prostate cancer after radical prostatectomy. This method can further be used for a visual documentation of the tumor stage independent of changes in the TNM classification. The method is inexpensive and practicable and can therefore be applied in routine surgical pathology.

De novo reconstitution of a functional mammalian urinary bladder by tissue engineering.

Human organ replacement is limited by a donor shortage, problems with tissue compatibility, and rejection. Creation of an organ with autologous tissue would be advantageous. In this study, transplantable urinary bladder neo-organs were reproducibly created in vitro from urothelial and smooth muscle cells grown in culture from canine native bladder biopsies and seeded onto preformed bladder-shaped polymers. The native bladders were subsequently excised from canine donors and replaced with the tissue-engineered neo-organs. In functional evaluations for up to 11 months, the bladder neo-organs demonstrated a normal capacity to retain urine, normal elastic properties, and histologic architecture. This study demonstrates, for the first time, that successful reconstitution of an autonomous hollow organ is possible using tissue-engineering methods.

[Interstitial cystitis. An important differential diagnosis]. / Interstitielle Zystitis. Eine wichtige Differentialdiagnose.

Interstitial cystitis (IC) is a chronic, debilitating inflammatory disease of the urinary bladder, characterized by chronic pelvic pain, urgency/frequency symptoms, and decrease of the functional bladder capacity. Both the etiology and pathogenesis of the condition that predominantly affects women are still not fully understood. Thus, a causal therapeutic approach still does not exist. IC remains a strict diagnosis of exclusion; distinct histopathological findings within the bladder wall are frequently found, although they are not pathognomonic. The diagnostic criteria elaborated by the NIH are helpful in clinical research; their dogmatic utilization will however lead to an underdiagnosis of IC in 60% of the patients. IC-specific symptom questionnaires and validated symptom scales help the physician to assess the therapeutic response during the follow-up of the patients.

[Treatment mapping of prostate cancer in DVPZ prostate centers in Germany]. / Versorgungsabbild zum Prostatakarzinom in DVPZ-Prostatazentren in Deutschland.

BACKGROUND: In prostate centers of the Governing Body of German Prostate Centers (DVPZ, Dachverband der Prostatazentren Deutschlands e.V.) treatment data from 3 university clinics, 21 treatment clinics, 3 private clinics and 330 general practitioners incorporated under 22 certificates are collated, in order to document the quality and type of cross-sectoral and interdisciplinary treatment, in particular of prostate cancer (PCA) patients. METHODS: This analysis is based on the DVPZ UroCloud data sets from 20 July 2015. The UroCloud reflects the web-based chronological disease development and quality parameters. For the descriptive analysis of particular key figures, available complete data sets were selected. RESULTS: Of the centers 22 held a valid certificate and fulfilled all required case numbers and structural prerequisites at the primary certification or recertification. In three cases a reauditing led to requirements before certification. Since 2005 a total of 9650 PCA patients have been pseudonymized and followed up (41,247 follow-up forms, 4.3 forms per patient). In 2014 the median number of newly documented PCA patients was 61 per center (minimum 7 and maximum 295). Radical prostatectomy (RP) dominated with 4491 (56 %) cases followed by primary hormonal therapy (1210 cases, 15 %), irradiation (809, 10 %) and non-interventional therapy, such as active surveillance (AS) or watchful waiting (WW) in 760 cases (10 %). A prostate-specific antigen (PSA) reduction was documented in 50 % of the patients with a preoperative PSA value > 20, in 60 % of pT4 tumors and in 50 % of patients with a tumor Gleason score of 9-10. A positive incision margin (R+) was found in in 15 % of pT2 stages, 41 % of pT3 stages and 85 % of pT4 stages. A secondary intervention was documented in 6.5 % of RP. CONCLUSION: The DVPZ certificate reflects the complete spectrum of treatment of PCA patients. The strength of the certificate lies in the documentation of patient development and a simultaneous collation of quality parameters.

Bladder augmentation using allogenic bladder submucosa seeded with cells.

OBJECTIVES: The search for a suitable material to reconstruct the genitourinary tract has been a challenging task. Bowel has been widely used for urinary tract reconstruction, despite its subsequent complications. We investigated the possibility of using allogenic bladder submucosa, a tissue consisting of nonimmunogenic acellular collagen, either with or without cells, as a material for bladder augmentation. METHODS: Partial cystectomies were performed in 10 beagle dogs. Both urothelial and smooth muscle cells were harvested and expanded separately in 5 animals. The allogenic bladder submucosa obtained from sacrificed dogs was seeded with muscle cells on one side and urothelial cells on the opposite side. All beagles underwent cruciate cystotomies on the bladder dome. Augmentation cystoplasty was performed with the allogenic bladder submucosa seeded with cells in 5 animals and with the allogenic bladder submucosa without cells in 5. The augmented bladders were retrieved 2 and 3 months after augmentation. RESULTS: Bladders augmented with the allogenic bladder submucosa seeded with cells showed a 99% increase in capacity compared with bladders augmented with the cell-free allogenic bladder submucosa, which showed only a 30% increase in capacity. All dogs showed a normal bladder compliance, as evidenced by urodynamic studies. Histologically, all retrieved bladders contained a normal cellular organization consisting of a urothelial lined lumen surrounded by submucosal tissue and smooth muscle. Immunocytochemical analyses confirmed the urothelial and muscle cell phenotype and showed the presence of nerve fibers. CONCLUSIONS: These results show that allogenic bladder submucosa seeded with cells appears to be an excellent option as a biomaterial for bladder augmentation.

Impact of free prostate-specific antigen on discordant measurement results of assays for total prostate-specific antigen.

OBJECTIVES: To determine why various assays for total PSA (t-PSA) produce discordant results in identical serum samples. METHODS: A total of 84 sera from 40 patients with histologically confirmed benign prostatic hyperplasia and from 44 patients with untreated prostate cancer were analyzed with seven assays for t-PSA and the Hybritech research assay for free prostate-specific antigen (f-PSA). Comparison between assays was performed by linear regression of the t-PSA concentrations as well as between the t-PSA concentrations and the f/t-PSA ratios. RESULTS: The coefficients of correlation for the investigated assays versus Hybritech Tandem-E range from 0.96 to 0.99. Nevertheless average PSA concentrations differed significantly from the Tandem-E assay in all assays. Despite a good correlation, some assays showed a regression line with a slope notably different from 1. In these assays, elevated concentrations were observed in sera with a high proportion of f-PSA. CONCLUSIONS: The study illustrates a significant and clinically relevant discordance between reported t-PSA concentrations for identical samples, depending on the assay used and on the contents of f-PSA in the sample. The interpretation of t-PSA concentrations requires awareness of the applied assay as well as the establishment of an assay-specific reference range in order to avoid inappropriate clinical consequences, such as unnecessary biopsies. Respective details must be contained in the laboratory reports. A change of assays without specifically reassessing previously valid reference ranges or the uncritical use of a customarily applied limit of < 4 ng/mL will otherwise be harmful to the patient.

Radical prostatectomy: survival outcome and correlation to prostate-specific antigen levels.

BACKGROUND: This paper reviews a 10-year experience with radical retropubic prostatectomy (RP) focussing on survival outcome related to pre- and postoperative levels of prostate-specific antigen (PSA). PATIENTS AND METHODS: 739 patients who underwent RP between 1987 and 1998 were prospectively investigated. Kaplan-Meier analyses were performed and correlated to pre- and postoperative PSA concentrations. RESULTS: In a follow up period of 11 years duration, (mean 3 yrs.) 57 of 739 patients died (20 from prostate disease progression, 37 from other causes). Correlation between low pre-operative PSA and pathological organ-confinement was significant (p < 0.001). Of 175 patients with PSA progression, 53 (30%) had never reached undetectable levels of PSA. 57% of PSA relapses were detected during the first year, and 3% later than 5 years post-operatively. Kaplan-Meier analysis yielded an average 3 years advantage in estimated prostate-cancer-specific survival when pre-operative PSA levels were below 50 ng/ml. Overall, prostate-cancer-specific and PSA-free 5-year survival-rates were 88%, 96% and 67% respectively. CONCLUSIONS: Survival-rates after RP are high even in conjunction with unfavourable PSA outcome. Merely one third of deaths resulted from prostate cancer, since men at risk frequently suffer from concomitant diseases that affect survival.

The impact of intraoperative manipulation of the prostate on total and free prostate-specific antigen.

OBJECTIVES: It is well documented that mechanical manipulation of the prostate can elevate total PSA (t-PSA) levels in serum. However, less is known about its effects on free PSA (f-PSA) and the free-to-total PSA ratio (f/t-PSA). We therefore examined the impact of prostate manipulation on t-PSA and f-PSA during surgical procedures involving the prostate. METHODS: Intraoperative blood samples for t-PSA and f-PSA measurement (Hybritech) were collected every 15 min during 14 radical retropubic prostatectomies (RRP) and 10 radical cystoprostatectomies (RCP). RESULTS: Prostatic manipulation induced significant elevations in t-PSA and f-PSA during RRP and RCP. Postmanipulatory peaks were markedly higher for f-PSA than for t-PSA. The mean maximum f-PSA levels showed a 4.3- (RRP) and 7.9-fold (RCP) increase, followed by a rapid decline after prostate removal. t-PSA increased 1.2- (RRP) and 1.3-fold (RCP), and declined more slowly. Postmanipulatory f/t-PSA ratios also increased significantly, reaching mean elevations of +0.29 and +0.28 over preoperative ratios during RRP and RCP, respectively. CONCLUSIONS: Prostate manipulation can induce transient increases in t-PSA, f-PSA and f/t-PSA in benign and malignant prostates. The extent of these alterations and their course over time must be taken into account when postmanipulatory changes in PSA forms are investigated. Timing of postmanipulatory venipunctures and the molar response ratio of t-PSA assays used (equimolar versus nonequimolar) seem to have substantial impact on the results of such studies.

[Alternative and complementary therapeutic measures in interstitial cystitis]. / Alternative und additive Therapieverfahren bei interstitieller Zystitis.

Alternative therapies are gaining more and more popularity. Mostly, these methods are demanded by patients who are not effectively relieved by allopathy. This review points out alternative and additive methods that have been repeatedly described as effective as additional supportive treatments of interstitial cystitis.

[Open surgical therapy of interstitial cystitis]. / Offen-chirurgische Therapie der interstitiellen Zystitis.

Treatment of IC is one of the most difficult therapeutic challenges in urology, frequently resulting in frustration for both patient and therapist. Many urologists believe that conservative treatment should not be unnecessarily prolonged in severe cases with low bladder capacity, since cystectomy may provide immediate and permanent relief for the suffering patient. However, it remains unclear which surgical approach and technique is the most suitable. Generally three different techniques are performed: supratrigonal cystectomy; radical cystectomy, saving only the bladder neck; and, finally, radical cystectomy combined with excision of the urethra. All three techniques require substitution of the excised bladder tissue with bowel segments.

[Different determination methods make interpretation of prostate-specific antigen more difficult]. / Unterschiedliche Bestimmungsverfarhen erschweren die Interpretation des prostataspezifischen Antigens.

The availability of numerous different assays for the determination of prostate-specific antigen (PSA) hs created substantial problems in the interpretation of PSA concentrations. Presently more than 40 assays are commercially promoted within the German market. The majority of the recently released assays claim the commonly used reference range (< 4 ng/ml) although this has no always been verified. Some companies entirely avoid the specification of reference ranges, others derive the data from very small cohorts. Reference ranges established with sera of young males or even with an unknown proportion of female sera are not valid in assessing the specificity of PSA assays to detect prostate cancer among male individuals between 50 and 80 years of age. Some companies recommend not to apply their assay for diagnostic purposes limit its use to the follow-up of patients previously diagnosed but to as having prostate cancer. This warning usually remains just as unknown to the urologist as the name of the assay used. Since PSA concentrations may vary in identical samples by a factor of 2, depending on the assay used, the clinician interpreting the results needs to be aware of the method applied and must have detailed information about the assay-specific reference range. Without this information, PSA loses its valuable diagnostic and prognostic features. Apart from avoidable worries on the patient's part, evidence of prostate cancer may be missed or unnecessary biopsies may be performed.

[Diagnosis of interstitial cystitis]. / Diagnostik der interstitiellen Zystitis.

Interstitial cystitis (IC) represents a rare and complex inflammatory bladder condition in which diagnostics can be challenging. Strict NIH criteria for its diagnosis were designed for research purposes. Their routine application would miss large proportions of IC patients. When IC is suspected, history and physical exam are followed by an evaluation of long-term voiding diaries. Large voided volumes (functional capacity > 250 cc) or longer micturition intervals (> 2 h.), absence of nocturia or symptom-free periods reduce the likelihood of IC. Further exclusion diagnostics include urine tests (infection), cytology (in-situ carcinoma), ultrasound (calculi, bulks, anomalies) and urodynamics in selected cases. Bladder capacity measurements under sedoanalgesia are of limited value, since functional low-volume bladders can be mechanically extendable. Cystoscopy under general anesthesia represents the diagnostic standard procedure for IC during which 90% of IC-patients present with characteristic mucosal glomerulations after bladder distension. Biopsies are recommended for exclusion of malignancy. Potassium-leak testing plays no relevant role in routine diagnostics due to its poor sensitivity. Similarly, complex determinations of novel IC markers (histamine, tryptase, cytokines, growth factors, substance P, nitric oxide) are of no relevance in clinical settings and should be restricted to research projects.

[Oral therapy of interstitial cystitis]. / Orale Therapie der interstitiellen Zystitis.

Up to now there is no specific treatment targeting the ultimate cause of interstitial cystitis (IC), since its pathogenesis and etiology are still unknown. Most studies focussing on oral medication have not been randomized, double-blinded or placebo-controlled. Numerous case reports and intent-to-treat trials are lacking a systematic approach and do not meet evidence-based medicine criteria. Consequently there is as yet no standard oral therapy available for the treatment of IC. However, only a few oral substances have shown a potential to improve symptoms such as frequency and pain. The best results were obtained from monotherapeutic use of pentosanpolysulfate, amitriptylin and hydroxycin. The true benefit of these substances alone should be compared to analgesics and anticholinergics in the course of controlled clinical trials.

Diagnosis and staging of prostatic carcinoma: what is really necessary?

Diagnosis and staging of prostatic carcinoma should be considered in men in whom treatment with curative intent is possible. The primary tools for detection of cancer are digital rectal examination (DRE) and serum prostate-specific antigen (PSA), whereas transrectal ultrasonography is best used to guide the needle for biopsy. Staging should be based on the TNM system. The most reliable staging methods include a combination of DRE, PSA and systematic biopsies for local tumor extension, pelvic lymphadenectomy for regional lymph nodes, and PSA and bone scintigraphy for distant metastases. Computed tomography and magnetic resonance imaging are not necessary in most cases.

Changes in movement characteristics of human spermatozoa along the length of the epididymis.

It has been established in laboratory mammals that sperm motility and fertilizing capacity develop during epididymal transit, but sperm maturation along the human epididymis is less well characterized. Spermatozoa were prepared from 5 regions of 8 epididymides from 8 prostatic carcinoma patients undergoing castration and from 8 epididymal spermatocoeles located adjacent to the head of the epididymides and the testes of 5 patients. Sperm movement was characterized by computer-aided sperm analysis (CASA), and percentage motility was estimated by conventional methods. The efferent ducts and spermatocoeles contained the same percentage of motile spermatozoa with similar kinematics. Percentage motility increased from 22.9 +/- 4.8 (mean +/- SEM) in the efferent ducts to a maximum of 68.3 +/- 7.9 in either the mid- or distal corpus epididymidis and declined in the cauda region. Straight line velocity increased from 20.3 +/- 3.7 microns/sec to reach a plateau value of 44.0 +/- 5.3 microns/sec in the mid-corpus epididymidis; this was more marked than the increase in curvilinear velocity, although the trend was the same. Similar trends in linearity and straightness of the swim paths were not accompanied by any significant changes in the amplitude of lateral head displacement. This objective quantification of sperm movement documents the maturation of sperm motility in the human epididymis, confirming that this maturation pattern is similar to that in other mammals.

Does the success of ureterointestinal implantation in orthotopic bladder substitution depend more on surgeon level of experience or choice of technique?

PURPOSE: We attempted to determine the relative risk of ureterointestinal anastomosis using 2 antireflux techniques of orthotopic bladder substitution, and we assessed the degree to which success is determined by surgeon experience. MATERIALS AND METHODS: A total of 120 patients underwent surgery, including 74 with the Hautmann (Le Duc) technique and 46 with a somewhat modified Studer (Nesbit/Studer) technique. The urologists who performed the operations were classified as expert, skilled and learner. Evaluation was done retrospectively. All patients in the Studer group, except 3 who died and 1 who was lost to followup, were monitored a minimum of 12 months. RESULTS: There was a 20.4% rate of nonneoplastic obstructions in the 142 ureters reimplanted with the Le Duc technique (Hautmann group). The variation in obstruction rates of 16.7, 18.2 and 25%, respectively, for expert, skilled and learning surgeons was statistically insignificant. Only 3 nonneoplastic obstructions (3.6%) developed in the 83 ureters reimplanted with the Nesbit/ Studer technique (Studer group). The variation in obstruction rates of 5.1, 0 and 3.6%, respectively, for expert, skilled and learner surgeons was statistically insignificant. CONCLUSIONS: The Nesbit/Studer technique results in a generally lower rate of ureterointestinal anastomotic stricture than the Le Duc technique. Using the Le Duc technique there was no statistically significant correlation between incidence of obstruction and surgeon level of experience, indicating that obstruction with this technique probably arises from other factors.